This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. Primary support for the subproject and the subproject's principal investigator may have been provided by other sources, including other NIH sources. The Total Cost listed for the subproject likely represents the estimated amount of Center infrastructure utilized by the subproject, not direct funding provided by the NCRR grant to the subproject or subproject staff. The goal of the application is to develop a novel therapeutic vaccine to Epstein-Barr virus (EBV) and its associated malignancies. EBV infection is responsible for the majority of AIDS-associated lymphomas. We propose to target the viral-encoded protein, EBNA1, which is the only viral protein consistently expressed in all EBV-associated malignancies. The vaccine will incorporate the fusion of the HSV gD protein to EBNA1 to overcome a negative regulatory arm of the adaptive immune response that has been implicated in tumor-associated immune escape. The vaccine vector will be derived from the E1-deleted adenoviral vectors based on the chimpanzee-serotype 68 (AdC68) to eliminate background immunogenicity to more common human serotypes. The vaccine will be tested in rhesus macaques, using the rhesus lymphocryptovirus (rhLCV) as the most appropriate animal model for EBV lymphomagenesis.